British MPs resoundingly rejected Prime Minister Theresa May's Brexit deal for a second time on Tuesday, plunging the country into further uncertainty just 17 days before it is due to split from the European Union.

The House of Commons voted 391-242 against the divorce deal, even after May secured further guarantees from Brussels over its most controversial elements.

The move risks unleashing economic chaos, as Britain is scheduled to end ties with its biggest trade partner after 46 years on March 29, no matter what.

Appearing before MPs in a voice half-breaking due to a cold, May defiantly vowed to fight on, saying she "profoundly" rejected the outcome.

"The deal we've negotiated is the best and indeed the only deal," she told the hushed chamber moments after the vote.

May promised to allow MPs to vote on a "no deal" option on Wednesday and, if that is rejected as expected, to decide on Thursday whether to ask the EU to delay Brexit.

She said parliament faced "unenviable choices" if it voted for an extension, including revoking Brexit, holding a second referendum or leaving with another deal.

However, eurosceptics believe the current deal is so bad that it is worth the risk of leaving with no plan.

The latest vote comes two years after Britain set the clock ticking on its departure from the EU following a highly divisive referendum in 2016.

Michel Barnier, the EU chief Brexit negotiator, said Brussels had nothing more to offer and must now brace for the possibility of a messy divorce.

"The EU has done everything it can to help get the Withdrawal Agreement over the line," Barnier tweeted.

"The impasse can only be solved in the #UK. Our 'no-deal' preparations are now more important than ever before."

But a spokeswoman for European Commission chief Jean-Claude Juncker said EU members would consider a "reasoned request" for a Brexit delay.

Jeremy Corbyn, leader of the main opposition Labour party who has been trying force snap elections, said May must now admit that her government's overarching strategy had failed.

"Their deal, their proposal, the one the prime minister's put, is clearly dead," Corbyn said, calling on her to change negotiate for a softer Brexit to keep close economies ties with the EU.

- Not a single change -

After MPs first rejected the 585-page Brexit deal in January, May promised changes to the hated backstop plan which is intended to keep open the border with EU member Ireland.

Weeks of talks failed to make a breakthrough, but May made a last-minute trip to Strasbourg to meet EU leaders on the eve of the vote.

She announced she had secured the promised "legally binding changes" to the backstop, which would keep Britain in the EU's customs union if and until a new way was found to avoid frontier checks.

Hours later, however, Attorney General Geoffrey Cox said the additions would not completely allay MPs fears of being trapped in the arrangement forever.

It did not take long for Brexit-supporting MPs in May's Conservative party, and her allies, Northern Ireland's Democratic Unionist Party (DUP), to declare their opposition.

Some eurosceptics did change their mind, urging their colleagues not to risk everything.

Former minister Edward Leigh said: "You may not like the deal, it's not perfect, but it delivers Brexit and let's go for it."

But the margin of Tuesday's defeat was not substantially smaller than the 230-vote thumping the plan suffered on January 15.

The pound, which has been highly volatile since the 2016 referendum, initially rose after the vote but then sank against both the euro and dollar.

- 'No third chance' -

The backstop is designed to protect the peace process in Northern Ireland, which involved the removal of border checks with EU member Ireland.

Brexit supporters wanted a unilateral way out of it, or a time limit to the arrangement, but the EU said this would make it worthless.

But leaders across Europe also united behind a message that this was the best and final offer Britain could expect.

"There will be no third chance," Juncker said after his talks on Monday with May.

If MPs vote against a no-deal exit on Wednesday, and want to postpone Brexit, the other 27 EU nations would need to agree.

Their leaders will meet in Brussels for a summit on March 21-22.

But any postponement may have to be short-lived.

Juncker on Monday said Brexit "should be complete before the European elections" at the end of May.